Para-aortic lymph node surgical staging in locally-advanced cervical cancer: comparison between robotic versus conventional laparoscopy.
- 作者列表："Loverix L","Salihi RR","Van Nieuwenhuysen E","Concin N","Han S","van Gorp T","Vergote I
OBJECTIVE:With the expansion of the use of minimally invasive surgical techniques within the field of gynecological oncology, a robot assisted procedure seems to be an attractive technique for para-aortic lymph node sampling. The aim of this study was to compare robotic versus conventional laparoscopic para-aortic lymphadenectomy in patients with locally advanced cervical cancer. METHODS:In this monocentric retrospective study, we included patients with locally-advanced cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2-IVA or IB1 with suspicious pelvic lymph nodes), who underwent a para-aortic lymphadenectomy up to the inferior mesenteric artery between December 1994 and December 2016 (robotic technique starting from December 2012). RESULTS:A total of 217 patients were included in the study (robotic, n=55 vs laparoscopic, n=162). When comparing conventional laparoscopic versus robotic para-aortic lymphadenectomy, the median age was 48 versus 49 years and the median body mass index was 24.4 vs 24.7 kg/m2, respectively. In the robotic or laparoscopic group, 85% and 83% were squamous carcinomas, respectively. Patients who underwent a robotic procedure had a higher American Society of Anesthesiologists (ASA) score (ASA2: 62% vs 56%, ASA3: 20% vs 2%, p<0.001), more prior major abdominal surgery (18% vs 6%, p=0.016), less estimated blood loss (median, 25 mL vs 62.5 mL, p<0.001), more para-aortic lymph nodes removed (11 vs 6, p<0.001), shorter postoperative stay (1.8 vs 2.3 days, p=0.002), and a higher, but non-significant, rate of metastatic para-aortic lymph nodes (13% vs 5%, p=0.065) compared with the laparoscopic procedure, respectively. There was no difference in complication rates between the two approaches. The most frequent complications were grade I and grade II according to the Clavien Dindo classification. No difference was observed in progression-free survival between robotic and laparoscopic para-aortic lymphadenectomy after 2 years (both groups 66%) (p=0.472). Also, 2 year overall survival was similar between the groups (77% vs 81% for robotic vs conventional laparoscopy group, respectively) (p=0.749). CONCLUSION:Robotic para-aortic lymphadenectomy in patients with locally-advanced cervical cancer resulted in better perioperative outcomes and similar survival outcomes when compared with a conventional laparoscopic approach.
目的: 随着微创手术技术在妇科肿瘤领域的应用扩大，机器人辅助手术似乎是主动脉旁淋巴结取样的一种有吸引力的技术。本研究的目的是比较机器人与传统腹腔镜主动脉旁淋巴结切除术在局部晚期宫颈癌患者中的应用。 方法: 在这项单中心回顾性研究中，我们纳入了局部晚期宫颈癌患者 (国际妇产科联盟 (FIGO) 2009 期 IB2-IVA 或 IB1，伴有可疑盆腔淋巴结)。1994年12月至 2016年12月接受主动脉旁淋巴结切除术直至肠系膜下动脉 (机器人技术从 2012年12月开始)。 结果: 共有 217 例患者纳入研究 (机器人，n = 55 vs 腹腔镜，n = 162)。当比较传统腹腔镜和机器人主动脉旁淋巴结切除术时，中位年龄分别为 48 岁和 49 岁，中位体重指数分别为 24.4 和 24.7 kg/m2。在机器人或腹腔镜组中，鳞癌分别为 85% 和 83%。接受机器人手术的患者美国麻醉医师协会 (ASA) 评分较高 (ASA2: 62% vs 56%，ASA3: 20% vs 2%，p<0.001),既往腹部大手术较多 (18% vs 6%，p = 0.016)，估计失血量较少 (中位数，25 ml vs 62.5 ml，p<0.001),切除的主动脉旁淋巴结更多 (11 vs 6，p<0.001)，术后住院时间更短 (1.8 vs 2.3 天，p = 0.002)，更高，但不显著,与腹腔镜手术相比，主动脉旁淋巴结转移率分别为 13% 和 5%，p = 0.065。两种入路的并发症发生率无差异。根据 Clavien Dindo 分类，最常见的并发症为 I 级和 II 级。2 年后，机器人和腹腔镜主动脉旁淋巴结清扫术的无进展生存率无差异 (两组均为 66%) (p = 0.472)。同样，两组之间的 2 年总生存率相似 (分别为机器人组和传统腹腔镜组分别为 77% 和 81%) (p = 0.749)。 结论: 与传统腹腔镜手术相比，机器人主动脉旁淋巴结清扫术治疗局部晚期宫颈癌患者具有更好的围手术期结局和相似的生存结局。
METHODS::Altered aerobic glycolysis is an important feature of cancer cell energy metabolism, known as the Warburg effect. Cervical cancer is one of the most common causes of cancer death in females. However, the roles of aerobic glycolysis in the development of cervical cancer are still poorly defined. Here, we identified a transcription factor (TF), ETS-related gene (ERG), as a new regulator of cancer progression and the glycolysis process in cervical cancer. In this study, we found that ectopic expression of ERG enhanced the capacity of aerobic glycolysis and increased glucose uptake, lactate production, and ATP generation. ERG overexpression increased and ERG knockdown decreased the anchorage independent cell growth and cell invasion in cervical cancer cells. Mechanistically, we propose that ERG regulates the expression of hexokinase 2 (HK2) and phosphoglycerate kinase 1 (PGK1) in the glycolytic pathway by directly binding to their promoters. A gain-of-function study showed that the knockdown or overexpression of HK2 and PGK1 abolished the increased or decreased aerobic glycolysis and cervical cancer progression induced by stable ectopic expression or depletion of ERG, respectively. Taken together, our findings suggest that ERG plays a potential role in the progression of cervical cancer, and could serve as a novel biomarker and potential therapeutic target in cervical cancer.
METHODS:INTRODUCTION:Australia has recently implemented major changes in cervical cancer prevention policies including introduction of primary human papillomavirus (HPV) screening starting at age 25, and replacement of the quadrivalent HPV vaccine with the nonavalent vaccine in the national school-based program. We assessed the feasibility and utility of conducting HPV testing in residual clinical specimens submitted for routine Chlamydia trachomatis screening, as a means of tracking HPV vaccine program impact among young sexually active women. METHODS:De-identified residual specimens from women aged 16-24 years submitted for chlamydia testing were collected from three pathology laboratories in Victoria and New South Wales. Limited demographic information, and chlamydia test results were also collected. Patient identifiers were sent directly from the laboratories to the National HPV Vaccination Program Register, to obtain HPV vaccination histories. Samples underwent HPV genotyping using Seegene Anyplex II HPV 28 assay. RESULTS:Between April and July 2018, 362 residual samples were collected, the majority (60.2%) of which were cervical swabs. Demographic data and vaccination histories were received for 357 (98.6%) women (mean age 21.8, SD 2.0). Overall, 65.6% of women were fully vaccinated, 9.8% partially, and 24.7% unvaccinated. The majority (86.0%) resided in a major city, 35.9% were classified in the upper quintile of socioeconomic advantage and chlamydia positivity was 7.8%.The prevalence of quadrivalent vaccine-targeted types (HPV6/11/16/18) was 2.8% (1.5-5.1%) overall with no differences by vaccination status (p = 0.729). The prevalence of additional nonavalent vaccine-targeted types (HPV31/33/45/52/58) was 19.3% (15.6-23.8%). One or more oncogenic HPV types were detected in 46.8% (95% CI 41.6-52.0%) of women. CONCLUSIONS:HPV testing of residual chlamydia specimens provides a simple, feasible method for monitoring circulating genotypes. Applied on a larger scale this method can be utilised to obtain a timely assessment of nonavalent vaccine impact among young women not yet eligible for cervical screening.
METHODS::Human papillomavirus (HPV) type 58 is the third most commonly detected HPV type in cervical cancer among Eastern Asians. Our previous international epidemiological studies revealed that a HPV58E7 natural variant, T20I/G63S (designated as V1), was associated with a higher risk of cervical cancer. We recently showed that V1 possesses a greater ability to immortalise and transform primary cells, as well as degrading pRB more effectively than the prototype and other common variants. In this study, we performed a series of phenotypic and molecular assays using physiologically relevant in vitro and in vivo models to compare the oncogenicity of V1 with that of the prototype and other common natural variants. Through activation of AKT and K-Ras/ERK signalling pathways, V1 consistently showed greater oncogenicity compared with prototype and other variants, as demonstrated by increased cell proliferation, migration and invasion, as well as induction of larger tumours in athymic nude mice. This study complements our previous epidemiological and molecular observations pinpointing the higher oncogenicity of V1 compared with prototype and all other common variants. Since V1 is more commonly found in Eastern Asia, our report provides insight into the design of HPV-screening assays and selection of components for HPV vaccines in this region.IMPORTANCE Epidemiological studies have revealed that a wild type variant of HPV58 carrying an E7 variation, T20I/G63S (V1), is associated with a higher risk of cervical cancer. We previously reported that this increased oncogenicity could be the result of its greater ability to degrade pRB, thereby leading to an increased ability to grow in an anchorage-independent manner. In addition to this, this report further showed that this HPV variant induced activation of AKT and K-Ras/ERK signalling pathways, thereby, explaining its genuine oncogenicity in promoting cell proliferation, migration, invasion, and formation of tumours, all to a greater extent than prototype HPV58 and other common variants.